The structure of SENP1-SUMO-2 complex suggests a structural basis for discrimination between SUMO paralogues during processing

The SUMO (small ubiquitin-like modifier)-specific protease SENP1 (sentrin-specific protease 1) can process the three forms of SUMO to their mature forms and deconjugate SUMO from modified substrates. It has been demonstrated previously that SENP1 processed SUMO-1 more efficiently than SUMO-2, but di...

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Published inBiochemical journal Vol. 397; no. 2; pp. 279 - 288
Main Authors Shen, Lin Nan, Dong, Changjiang, Liu, Huanting, Naismith, James H, Hay, Ronald T
Format Journal Article
LanguageEnglish
Published England Portland Press Ltd 15.07.2006
Subjects
Amino Acid Sequence
Crystallography, X-Ray
Cysteine Endopeptidases
Endopeptidases - chemistry
Endopeptidases - physiology
Humans
Models, Molecular
Molecular Sequence Data
Protein Binding
Protein Conformation
Protein Structure, Tertiary
Small Ubiquitin-Related Modifier Proteins - chemistry
Small Ubiquitin-Related Modifier Proteins - physiology
Static Electricity
Substrate Specificity
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Summary:The SUMO (small ubiquitin-like modifier)-specific protease SENP1 (sentrin-specific protease 1) can process the three forms of SUMO to their mature forms and deconjugate SUMO from modified substrates. It has been demonstrated previously that SENP1 processed SUMO-1 more efficiently than SUMO-2, but displayed little difference in its ability to deconjugate the different SUMO paralogues from modified substrates. To determine the basis for this substrate specificity, we have determined the crystal structure of SENP1 in isolation and in a transition-state complex with SUMO-2. The interface between SUMO-2 and SENP1 has a relatively poor complementarity, and most of the recognition is determined by interaction between the conserved C-terminus of SUMO-2 and the cleft in the protease. Although SENP1 is rather similar in structure to the related protease SENP2, these proteases have different SUMO-processing activities. Electrostatic analysis of SENP1 in the region where the C-terminal peptide, removed during maturation, would project indicates that it is the electrostatic complementarity between this region of SENP1 and the C-terminal peptides of the various SUMO paralogues that mediates selectivity.
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1Present address: Centre for Interdisciplinary Research, School of Life Science, University of Dundee, Dundee, Scotland DD1 5EH, U.K.
The structural coordinates for SENP1 (sentrin-specific protease 1) and SENP1 complexed with SUMO-2 (small ubiquitin-like modifier 2) have been deposited in the Protein Data Bank under codes 2CKG and 2CKH respectively.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj20052030